Non-identical distribution pattern of epidermal growth factor and platelet-derived growth factor in the mouse uterus during the oestrous cycle and early pregnancy LOUAY JABER and FREDERICK W.K. KAN  Department of Anatomy and Cell Biology, Faculty of Medicine, Queen's University, Kingston, Ontario, Canada K7L 3N6 Received 29 August 1997 and in revised form 26 May 1998 Summary In the present study, we examined by immunohistochemistry the cell-speci®c distribution of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) in the mouse uterus during the oestrous cycle and throughout the ®rst 7 days of pregnancy. Paraf®n-embedded tissue samples were immunostained using the avidin±biotin peroxidase technique and then examined by light microscopy. Our results showed that immunostaining for EGF was detected in the stroma but not in the luminal or glandular epithelium. A high concentration of EGF was detected in the stroma around the time of embryo implantation at days 3, 4 and 5 of pregnancy. The implanted embryo at day 7 of gestation showed immunostaining for EGF between the ectoderm and endoderm layers. The cell distribution pattern for PDGF was found to be different from that observed with EGF. Luminal and glandular epithelia displayed PDGF immunostaining throughout the ®rst 7 days of pregnancy, with the highest intensity at days 4 and 5 of gestation. In contrast, no immunostaining was observed in the luminal and glandular epithelia at post-oestrus, dioestrus and pro-oestrus stages. However, a weak reaction started to appear at oestrus. The embryo at the blastocyst stage displayed a strong immunoreaction for antibody against PDGF. In addition, the decidual boundary zone surrounding the implanted embryo at days 5, 6 and 7 of gestation also showed an immunostaining for PDGF. The present observations demonstrate clearly the presence of EGF and PDGF in the mouse uterus in high concentrations at the peri-implantation period. Thus, our results, together with what is known about the effect of EGF and PDGF in controlling the growth, differentiation and activation of a variety of cell types, suggest a possible role for these growth factors during the preparation of the endometrium for implantation in controlling the proliferation activity of stromal and/or epithelial cells. # 1998 Chapman & Hall Introduction Epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) are two of several important polypeptides that play important roles in controlling the growth, differentiation and activation of a variety of cell types through their interactions with speci®c cell-surface receptors in their target tissues (Carpenter & Cohen, 1979; Ross et al., 1986; Fisher & Lakshmanan, 1990; Westermark, 1990). Epidermal growth factor has been implicated in several func- tions related to embryo development (Adamson et al., 1981; Wood & Kaye, 1989; Paria & Dey, 1990), whereas the predominant role of PDGF is to stimulate the proliferation of mesenchymal cells (Ross et al., 1986). Epidermal growth factor has been found to be present in the human uterus (Chegini et al., 1986, 1992; Hofmann et al., 1991) and placenta (Hofmann et al., 1991). In the uterus, EGF was localized by a histochemical method mainly to the stromal cells in the endometrium, and a faint or negative EGF immunoreaction was observed in the uterine epithe- lial cells (Hofmann et al., 1991). In the female reproductive tract, it has been shown that EGF has mitogenic effects on uterine cell proliferation in vitro (Tomooka et al., 1986) and that binding of EGF to rat uterine membrane increases gradually through the pre- and post-implantation periods (Chakraborty et al., 1988). Interestingly, a low level of EGF in the plasma, induced experimentally, has been reported to cause abortion in mice (Tsutsumi & Oka, 1987). Histochemical Journal 30, 711±722 (1998) 0018±2214 # 1998 Chapman & Hall  To whom correspondence should be addressed.